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In vivo and in vitro generation of a new altered HLA phenotype in melanoma‐tumour‐cell variants expressing a single HLA‐class‐I allele
Author(s) -
Real Luis Miguel,
Jimenez Pilar,
Cantón Julia,
Kirkin Alexei,
García Angel,
Abril Eduardo,
Zeuthen Jesper,
RuizCabello Francisco,
Garrido Federico
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980119)75:2<317::aid-ijc23>3.0.co;2-8
Subject(s) - human leukocyte antigen , melanoma , phenotype , allele , biology , in vivo , in vitro , genetics , cancer research , immunology , gene , antigen
A new HLA‐class‐I altered phenotype is described in melanoma. This phenotype is the result of a combination of HLA‐B‐locus down‐regulation and HLA‐haplotype loss. The alteration was found in 2 melanoma cell lines generated from 2 patients; one was derived from an in vivo lesion (FM37) and the other was obtained after in vitro immunoselection (R22.2). The R22.2 cell line was isolated from FM55P, a cell line derived from a primary melanoma, after in vitro treatment with a heterologous HLA‐A2‐restricted cytotoxic‐T‐lymphocyte (CTL) clone. Two additional cell lines from patient 55 were obtained from 2 s.c. metastases (FM55M1 and FM55M2). Iso‐electric focusing and flow‐cytometric studies showed a significant reduction in the expression of both HLA‐B alleles in all cell lines studied. The expression of HLA‐B‐locus products recovered completely after IFN‐γ treatment of FM55P, M1 and M2. In contrast, FM37 and R22.2 tumour cells showed an additional HLA defect: the absence of one HLA haplotype. Simple tandem‐repeat polymorphism markers spanning chromosome 6 showed that DNA from the 2 samples (FM37 and R22.2) showed loss of heterozygosity (LOH). In both cases, homozygosity was observed on 6p, which maps the HLA region, the final consequence being a tumour cell that expressed a single HLA‐class‐I allele (HLA‐A3 and HLA‐A1 respectively). FM37 cells may thus reflect the in vivo counterpart of resistance to lysis by HLA‐A2‐restricted tumour‐infiltrating lymphocytes. Int. J. Cancer 75:317–323, 1998. © 1998 Wiley‐Liss, Inc.